Abstract A14: The role of Livin in oncogenesis reveals a novel mode of gene regulation

Abstract A14 Acquired resistance to apoptosis is a hallmark of all types of cancer. The Inhibitor of Apoptosis Protein (IAP) family members is able to inhibit apoptosis induced by a variety of stimuli mainly by binding to and inhibiting caspases. We and others previously identified the IAP Livin. We further showed that Livin functions as a regulator of apoptosis that can undergo cleavage by effector caspases to produce a truncated form with paradoxical pro-apoptotic activity. In this study we describe the role of Single Nucleotide Polymorphism (SNP) in the regulation of Livin in normal and malignant cells and demonstrate how the 528 (C/T) SNP regulates Livin protein expression. We show that Livin is expressed in a non-random monoallelic manner as only the 528T allele is expressed in normal blood and in early-stage melanoma. In advanced melanoma, by mechanism of DNA overrepresentation, both 528T and 528C mRNA alleles of Livin are expressed, resulting in expression of the Livin protein. The variable expression of the Livin protein plays a major role in the survival of melanoma patients: We show that high Livin expression is an independent adverse prognostic marker. Importantly, we show that low-intermediate expression of Livin is associated with favorable prognosis in comparison to no Livin expression. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A14.